|
Topic Name: Holy Grail of hearing: True identity of pivotal hearing structure is revealed
Category: Electrical
Research persons: James F. Battey, M.D., Ph.D
Location: NIDCD/NIH, Building 31, Room 3C02, Bethesda, MD 20892, United States
Details
When a noise occurs,
such as a car honking or a person laughing, sound vibrations entering the ear
first bounce against the eardrum, causing it to vibrate. This, in turn, causes
three bones in the middle ear to vibrate, amplifying the sound. Vibrations from
the middle ear set fluid in the inner ear, or cochlea, into motion and a
traveling wave to form along a membrane running down its length. Sensory cells
(called hair cells) sitting atop the membrane ride the wave and in doing so,
bump up against an overlying membrane. When this happens, bristly structures
protruding from their tops (called stereocilia) deflect, or tilt to one side.
The tilting of the stereocilia cause pore-sized channels to open up, ions to
rush in, and an electrical signal to be generated that travels to the brain, a
process called
mechanoelectrical transduction.
Our ability to hear is
made possible by way of a Rube Goldberg-style process in which sound vibrations
entering the ear shake and jostle a successive chain of structures until, lo and
behold, they are converted into electrical signals that can be interpreted by
the brain. Exactly how the electrical signal is generated has been the subject
of ongoing research interest.
In a study published in the September 6 issue of the journal Nature, researchers
have shed new light on the hearing process by identifying two key proteins that
join together at the precise location where energy of motion is turned into
electrical impulses. The discovery, described by some scientists as one of the
holy grails of the field, was made by researchers at the National Institute on
Deafness and Other Communication Disorders (NIDCD), one of the
National Institutes of Health (NIH), and the
Scripps Research Institute in La Jolla, CA.
This team has helped solve one of the lingering mysteries of the field,? says
James F. Battey, Jr., M.D., Ph.D., director of the
NIDCD. ?The better we understand the pivotal point at which a person is able
to discern sound, the closer we are to developing more precise therapies for
treating people with hearing loss, a condition that affects roughly 32.5 million
people in the United States alone.?
When a noise occurs, such as a car honking or a person laughing, sound
vibrations entering the ear first bounce against the eardrum, causing it to
vibrate. This, in turn, causes three bones in the middle ear to vibrate,
amplifying the sound. Vibrations from the middle ear set fluid in the inner ear,
or cochlea, into motion and a traveling wave to form along a membrane running
down its length. Sensory cells (called hair cells) sitting atop the membrane
?ride the wave and in doing so, bump up against an overlying membrane. When this
happens, bristly structures protruding from their tops (called stereocilia)
deflect, or tilt to one side. The tilting of the stereocilia cause pore-sized
channels to open up, ions to rush in, and an electrical signal to be generated
that travels to the brain, a process called mechanoelectrical transduction.
Most scientists believe that the channel gates are opened and closed by
microscopic bridges called tip links that connect shorter stereocilia to taller
ones positioned behind them. If scientists could determine what the tip links
are made of, they will be one step closer to understanding what causes the
channel gates to open. This is no easy feat, however, because
stereocilia are extremely
small, scarce, and difficult to handle. Several proteins had been reported to
occur at the tip link in earlier studies, but results have been conflicting to
this point.
About Researcher
James F. Battey, M.D., Ph.D.
Director, NIDCD
Senior Investigator
G-protein Coupled Receptors' Section, NINDS
NIDCD/NIH
Building 31, Room 3C02
Bethesda, MD 20892
Phone: (301) 402-0900
Fax: (301) 402-1590
E-mail: batteyj@nidcd.nih.gov
Research Statement
The G-protein Coupled Receptors' Section is interested in elucidating the
structure, function, and regulation of the largest family of proteins in the
genome that mediate intracellular signaling. Our attention is focused primarily
on the bombesin receptor subfamily and candidate taste receptors.
Bombesin Receptor Family: Mammalian bombesin receptors
mediate a wide spectrun of physiologic processes, including hormone release,
smooth muscle contraction, and cell division. There are three different bombesin
receptors with distinct structural and pharmacologic properties: the gastrin-releasing
peptide receptor, the neuromedin B receptor, and bombesin receptor subtype 3. We
have used site-directed mutagenesis to define structural motifs critical for
ligand binding, G protein coupling, and receptor activity. At the present time,
we are using gene targeting strategies to determine the function of each
receptor in the context of an intact mouse. In addition, we are exploring the
role of phosphorylation and additional receptor binding proteins in regulating
receptor activity.
Taste Receptors: We are collaborating with
Dr. Susan
Sullivan's laboratory in creating a cDNA library enriched for cDNAs from
transcripts selectively expressed in taste cells. About 20,000 clones from this
library will be sequenced in an effort to identify novel molecules (receptors, G
protein subunits, effectors, channels, etc.) that are selectively expressed in
taste receptor cells. Candidate molecules will be assessed for their importance
in mediating sense of taste.
|
